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Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial.

ABSTRACT: BACKGROUND:Nodding syndrome is a poorly understood neurological disorder of unknown aetiology, affecting several thousand children in Africa. There has been a consistent epidemiological association with infection by the filarial parasite, Onchocerca volvulus and antibodies to leiomodin and DJ-1, cross-reacting with O.volvulus proteins, have been reported. We hypothesized that nodding syndrome is a neuro-inflammatory disorder, induced by antibodies to O.volvulus or its symbiont, Wolbachia, cross-reacting with human neuron proteins and that doxycycline, which kills Onchocerca through effects on Wolbachia, may be used as treatment. METHODS:This will be a two-arm, double-blind, placebo-controlled, randomised phase II trial of doxycycline 100?mg daily for six weeks in 230 participants. Participants will be patients' ages?8?years with nodding syndrome. They will receive standard of care supportive treatment. All will be hospitalised for 1-2?weeks during which time baseline measurements including clinical assessments, EEG, cognitive and laboratory testing will be performed and antiepileptic drug doses rationalised. Participants will then be randomised to either oral doxycycline (Azudox®, Kampala Pharmaceutical Industries) 100?mg daily or placebo. Treatment will be initiated in hospital and continued at home. Participants will be visited at home at 2, 4 and 6?weeks for adherence monitoring. Study outcomes will be assessed at 6, 12, 18 and 24-month visits. Analysis will be by intention to treat. The primary efficacy outcome measure will be the proportion of patients testing positive and the levels or titires of antibodies to host neuron proteins (HNPs) and/or leiomodin at 24?months. Secondary outcome measures will include effect of the intervention on seizure control, inflammatory markers, cognitive function, disease severity and quality of life. DISCUSSION:This trial postulates that targeting O.volvulus through drugs which kill Wolbachia can modify the pathogenic processes in nodding syndrome and improve outcomes. Findings from this study are expected to substantially improve the understanding and treatment of nodding syndrome. TRIAL REGISTRATION:Registered with clinicaltrials.gov ID: NCT02850913 on 1st August, 2016.

SUBMITTER: Idro R

PROVIDER: S-EPMC6402111 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial.

Idro Richard R Anguzu Ronald R Ogwang Rodney R Akun Pamela P Abbo Catherine C Mwaka Amos Deogratius AD Opar Bernard B Nakamya Phyellister P Taylor Mark M Elliott Alison A Vincent Angela A Newton Charles C Marsh Kevin K

BMC neurology 20190306 1

<h4>Background</h4>Nodding syndrome is a poorly understood neurological disorder of unknown aetiology, affecting several thousand children in Africa. There has been a consistent epidemiological association with infection by the filarial parasite, Onchocerca volvulus and antibodies to leiomodin and DJ-1, cross-reacting with O.volvulus proteins, have been reported. We hypothesized that nodding syndrome is a neuro-inflammatory disorder, induced by antibodies to O.volvulus or its symbiont, Wolbachia ...[more]

PMID: 30841858

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Dataset Information

Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial.

Publications

Doxycycline for the treatment of nodding syndrome (DONS); the study protocol of a phase II randomised controlled trial.

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